Reproducability and transferability of topological properties; experimental charge density of the hexapeptide cyclo-(<scp>D,L</scp>-Pro)_2–(<scp>L</scp>-Ala)_4 monohydrate

Dittrich, Birger; Koritsánszky, T.; Grosche, Manja; Scherer, Wolfgang; Flaig, Ralf; Wagner, Armin; Krane, H.‐G.; Kessler, Horst; Riemer, Christoph; Schreurs, Antoine M. M.; Luger, Peter

doi:10.1107/s0108768102005839

Cited by 51 publications

(43 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Given a well refined high-resolution structure, electrostatic properties may be calculated in different ways: directly by multipolar analysis or using DFT (this work) and͞or QM͞MM methods (34)(35)(36) or by using fragments experimentally (TRF; ref. 27 and this work) or theoretically calculated (37)(38)(39)(40)(41), or by point charge models such as AMBER (29), CHARMM (42), or GRASP (43). This paper has demonstrated that DFT quality potentials can be obtained quickly and almost routinely from high-resolution diffraction data (TRF).…”

Section: Resultsmentioning

confidence: 97%

Electrostatic complementarity in an aldose reductase complex from ultra-high-resolution crystallography and first-principles calculations

Muzet

Guillot

Jelsch

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

106

109

View full text Add to dashboard Cite

The electron density and electrostatic potential in an aldose reductase holoenzyme complex have been studied by density functional theory (DFT) and diffraction methods. Aldose reductase is involved in the reduction of glucose in the polyol pathway by using NADPH as a cofactor. The ultra-high resolution of the diffraction data and the low thermal-displacement parameters of the structure allow accurate atomic positions and an experimental charge density analysis. Based on the x-ray structural data, order-N DFT calculations have been performed on subsets of up to 711 atoms in the active site of the molecule. The charge density refinement of the protein was performed with the program MOPRO by using the transferability principle and our database of charge density parameters built from crystallographic analyses of peptides and amino acids. Electrostatic potentials calculated from the charge density database, the preliminary experimental electron density analysis, DFT computations, and atomic charges taken from the AMBER software dictionary are compared. The electrostatic complementarity between the cofactor NADP ؉ and the active site shows up clearly. The anchoring of the inhibitor is due mainly to hydrophobic forces and to only two polar interaction sites within the enzyme cavity. The potentials calculated by x-ray and DFT techniques agree reasonably well. At the present stage of the refinement, the potentials obtained directly from the database are in excellent agreement with the experimental ones. In addition, these results demonstrate the significant contribution of electron lone pairs and of atomic polarization effects to the host and guest mechanism.

show abstract

Section: Resultsmentioning

confidence: 97%

Electrostatic complementarity in an aldose reductase complex from ultra-high-resolution crystallography and first-principles calculations

Muzet

Guillot

Jelsch

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

106

109

View full text Add to dashboard Cite

show abstract

“…Atomic properties have also been used empirically to predict several experimental properties including for example, the pK a of weak acids from the atomic energy of the acidic hydrogen [96], a wide array of biological and physicochemical properties of the amino acids, including the genetic code itself, and the effects of mutation on protein stability [60], protein retention times [97], HPLC column capacity factors of high-energy materials [98], NMR spin-spin coupling constants from the electron delocalization indices [99,100], simultaneous consistent prediction of five bulk properties of liquid HF in MD simulation [101], classification of atom types in proteins with future potential applications in force-field design [60,[102][103][104], reconstructing large molecules from transferable fragments or atoms in molecules [60,[105][106][107][108][109][110][111][112][113][114][115][116][117][118][119] (see also Chapters 11 and 12), atomic partitioning of the molecular electrostatic potential [120][121][122], prediction of hydrogenbond donor capacity [123] and basicity [124], and to provide an atomic basis for curvature-induced polarization in carbon nanotubes and nanoshells [125].…”

Section: The Use Of Qtaim Atomic Propertiesmentioning

confidence: 99%

An Introduction to the Quantum Theory of Atoms in Molecules

Matta

Boyd

2007

The Quantum Theory of Atoms in Molecules

478

599

View full text Add to dashboard Cite

“…Cyclo-(dl-prolyl) 2 -(l-alanyl) 4 Monohydrate: The experimental charge density study of this cyclic hexapeptide by Dittrich et al [40] is based on 100 K synchrotron data and predicts a substantial and significant enhancement of 93(9) %. The Lorentz tensor approach using only point dipoles for the hexapeptide (i.e.…”

mentioning

confidence: 98%

Dipole Moment Enhancement in Molecular Crystals from X‐ray Diffraction Data

2007

View full text Add to dashboard Cite

Although reliable determination of the molecular dipole moment from experimental charge density analyses on molecular crystals is a challenging undertaking, these values are becoming increasingly common experimental results. We collate all known experimental determinations and use this database to identify broad trends in the dipole moment enhancements implied by these measurements as well as outliers for which enhancements are pronounced. Compelling evidence emerges that molecular dipole moments from X-ray diffraction data can provide a wealth of information on the change in the molecular charge distribution that results from crystal formation. Most importantly, these experiments are unrivalled in their potential to provide this information in such detail and deserve to be exploited to a much greater extent. The considerable number of experimental determinations now available has enabled us to pinpoint those studies that merit further attention, either because they point unequivocally to a considerable enhancement in the crystal (of 50 % or more), or because the experimental determinations suggest enhancements of 100 % or more--much larger than independent theoretical estimates. In both cases further detailed experimental and theoretical studies are indicated.

show abstract

Reproducability and transferability of topological properties; experimental charge density of the hexapeptide cyclo-(D,L-Pro)_2–(L-Ala)_4 monohydrate

Cited by 51 publications

References 15 publications

Electrostatic complementarity in an aldose reductase complex from ultra-high-resolution crystallography and first-principles calculations

Electrostatic complementarity in an aldose reductase complex from ultra-high-resolution crystallography and first-principles calculations

An Introduction to the Quantum Theory of Atoms in Molecules

Dipole Moment Enhancement in Molecular Crystals from X‐ray Diffraction Data

Contact Info

Product

Resources

About